The overall goal of this project is to study intermediates in the biochemical pathway that produces melanin and to study drugs affecting the release of pituitary releasing factors with the ultimate hope of applying this informatin to the control of melanoma. The approaches to bve employed include biochemical manipulations of murine and human melanomas being grown in long term tissue culture and in vivo studies of mice containing these transplanted tumor cells. The experiments to be performed will include addition of melanin precursors to the tissue culture cell lines and assaying their effects on 3H-TdR and 14C-leu incorporation. These drugs will include L-dopa, dopamine, and dopa methylester. In addition, an antidopamine drug, pimozide, will be investigated in a similar fashion. Internal controls will consist of counting cell numbers and assising cell viability using trypan blue exclusion criteria. Effects of these agents on the incorporation of 14C-leu and 3H-TdR will then be correlated withsimilar drug effects on mice following tumor inoculation. Pimozide is a potent inhibitor of the release of pituitary releasing factors, in addition to its anti-dopamine effect. Bromocriptine stimulates release of pituitary releasing factors. These neuroendocrine effects will be studied in vivo by investigating the effect on mouse survival following tumor transplantation when compared to control mice with tumor but receiving no drug. These studies may provide a rationale for the investigation of drugs efficting the neuroendocrine system in patients with melanoma.